BACKGROUND: Hand-foot-mouth disease (HFMD) is mainly caused by the infection of coxsackievirus A16. But recently several epidemics of HFMD with meningitis or myocarditis due to enterovirus 71 have been reported in Southeast Asia. It was necessary that the possibility of enterovirus 71 epidemic in Korea should be ruled out. This study was designed for the determination of causative agents of HFMD in Cheju province in the spring of 1998. METHODS: Serum specimens were collected from 45 pediatric patients with HFMD at Cheju Hankook Hospital in March and April,1998. Virus isolation was performed with RD cell culture through up to three passages. Reverse transcription-PCR and nucleotide sequencing were performed by the method of Oberste et al.(J Clin Microbiol 1999;37:1288-93). The serotypes of viral isolates were determined by BLAST program of National Center for Biotechnology Information, U.S.A. RESULTS: Virus could be isolates from 4 patients, whose age was ranged from 11 months to 3 years. All of 4 viral isolates showed about 430-bp product of RT-PCR using primers 011 and 012. The serotype showing the highest similarity with the nucleotide sequences of all of these viral isolates was coxsackievirus A16. CONCLUSIONS: The causative enteroviral agent of HFMD in Cheju province in the spring of 1998 was coxsackievirus A16. We could not detect enterovirus 71 from the patients' sera in Cheju Province in the spring of 1998.